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René spent his youth in the court of his grandfather René I of Anjou between Angers and Provence, succeeding to his father in Vaudémont in 1470 and, three years later, to his uncle as captain of Angers, senechal and governor of Anjou. In the same year he became Duke of Lorraine, which was at the time under the pressure of both Louis XI of France and Charles the Bold of Burgundy, with whom he initially allied. When the latter began to establish garrisons in Lorraine, however, René secretly allied with Louis (1474). Charles invaded the duchy and René was forced to quit Nancy (30 November 1475). He regained the city on 5 October the following year and moved to Switzerland to hire an army of Swiss mercenaries. With this force René defeated and killed Charles at the Battle of Nancy (5 January 1477), ending the Burgundian Wars. In 1476, upon the death of his grandmother, he became sole Count of Harcourt and Baron of Elbeuf.

Later, René got to bad terms with Louis, who had taken most of his heritage. He moved to Italy and defeated the Duke of Ferrara in the Battle of Adria as an ally of the Republic of Venice.

In 1480 René succeeded his grandfather as Duke of Bar while his mother was still living. In 1482 he conquered the prévôté of Virton, a part of the Duchy of Luxembourg, and annexed it to Bar. In 1484 Peter II, Duke of Bourbon, regent for the young King Charles VIII of France, formally installed him in the Duchy of Bar.[1] When his mother Yolande died in 1483, he succeeded her in her claims to the kingdoms of Naples and Jerusalem.

In 1485 René took part in the first phase of the so-called "Mad War", but prudentially retired after a while. In 1488 the Neapolitans offered him the crown of the Kingdom of Naples, and René set an expedition to gain possession of the realm; he was however halted by the new French king, Charles VIII, who intended to claim the realm himself.

In 1495, to settle a dispute with his second cousin, Jean IV de Rieux, over their grandmothers' inheritance, he ceded to Jean the county of Harcourt and its appurtenances, retaining only Elbeuf and Brionne, and receiving the county of Aumale.[2]

On his mother's side, he was a grandson of Isabella, Duchess of Lorraine. His father was a member of the Vaudémont family, a junior branch of the Lorraine ducal family, descending from John I, Duke of Lorraine. He was thus both heir-general and heir-male to the Duchy when he succeeded on the death of his cousin Nicholas in 1473.

On 9 September 1471 he married Jeanne d'Harcourt (d. 1488), Countess of Tancarville, but the marriage was annulled in 1485.